Another VEGF Inhibitor Shows Activity Against Kidney Cancer

PARIS, Oct. 30 -- Treatment with axitinib resulted in at least a partial response in nearly half of patients with cytokine-refractory metastatic kidney cancer, investigators in a multinational trial have found.
The investigational vascular endothelial growth factor (VEGF) inhibitor resulted in two complete responses and 21 partial responses in 52 patients, Olivier Rixe, M.D., of the University of Paris, and colleagues, reported in the November issue of The Lancet Oncology.
Additionally, they said, in 22 patients the disease stabilized for at least eight weeks, and in 13 patients, for 24 weeks or longer.
"The objective response and time to progression in our study suggest that axitinib might be a promising drug in the treatment of patients with metastatic renal-cell cancer; although a randomized controlled trial is needed to confirm this finding," the authors concluded.

Biological therapy with interferon alfa or interleukin-2 has only modest activity in good-risk patients with renal-cell carcinoma. Antiangiogenic therapies have improved survival in the disease, and two agents, sunitinib and sorafenib (also VEGF inhibitors) have been approved for treatment of metastatic renal-cell carcinoma.
Axitinib is an oral selective inhibitor of VEGF receptors 1, 2, and 3. Preclinical studies suggested that the agent had antitumor activity related to antiangiogenic effects, and phase 1 clinical investigation provided additional evidence of activity in patients with various advanced solid tumors.
Dr. Rixe and investigators in Europe and the United States continued the evaluation of the drug in a phase II trial involving patients with metastatic renal-cell carcinoma unresponsive to cytokine therapy. Treatment began at a dose of 5 mg twice daily. The dose could be titrated upward by 20% after eight weeks if a patient had no tumor response and no grade 2+ toxicity.
The primary endpoint was objective response. Secondary endpoints were response duration, time to progression, overall survival, safety, pharmacokinetics, and patient-reported health-related quality of life.
In an intention-to-treat analysis, axitinib resulted in an overall response rate of 44.2%. The median response duration was 23 months. However, 12 of 23 initial responders progressed with a response that lasted between 4.2 and 26.5 months. An additional 42.3% of patients had prolonged disease stabilization.
Four patients had early disease progression, and three had incomplete data. The median time to progression was 15.7 months, and the median overall survival was 29.9 months.
The most common treatment-related adverse events were diarrhea, hypertension, fatigue, nausea, and hoarseness. Thirty patients had treatment-related hypertension that resolved with antihypertensive therapy in 22 cases. Seven of the remaining eight patients had a history of hypertension.
Dr. Rixe disclosed that he has been a consultant to Pfizer and received honoraria for participation in Pfizer-supported activities. The study was supported by Pfizer. Primary source: The Lancet OncologySource reference: Rixe O, et al "Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study." Lancet Oncol 2007; 8: 975-984.